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在包含人类p53基因的基因组区域中DNA修复结构域的定义。

Definition of a DNA repair domain in the genomic region containing the human p53 gene.

作者信息

Tolbert D M, Kantor G J

机构信息

Department of Biological Sciences, Wright State University, Dayton, Ohio 45435, USA.

出版信息

Cancer Res. 1996 Jul 15;56(14):3324-30.

PMID:8764129
Abstract

The human p53 gene is repaired in UV (254 nm)-irradiated xeroderma pigmentosum group C (XP-C) cells as part of a large genomic region that is about twice the size of the gene. Surrounding genomic regions are not repaired. Through DNA cloning and measurements of DNA repair, we mapped the location of the repair domain, including the terminal regions, relative to the topological features of the gene. The domain includes only the DNA strand that is transcribed and extends in both 3' and 5' directions beyond the promoter and transcription termination sites. No transcriptional activity other than that associated with the p53 gene was detected. The results suggest that nontranscribed regions adjacent to the p53 transcribed regions are efficiently repaired in XP-C cells. This means that factors associated with transcription other than RNA polymerase II and the associated transcription repair coupling factor must also play a role in the selective repair process in XP-C cells. We also found that a DNA fragment that contains the p53 promoters is nearly twice as sensitive to cyclobutane pyrimidine dimer induction by UV irradiation than are the surrounding fragments, which have the expected sensitivity.

摘要

人类p53基因在紫外线(254nm)照射的着色性干皮病C组(XP - C)细胞中作为一个大约是该基因两倍大小的大基因组区域的一部分得到修复。周围的基因组区域未被修复。通过DNA克隆和DNA修复测量,我们绘制了修复区域相对于该基因拓扑特征的位置,包括末端区域。该区域仅包括被转录的DNA链,并且在3'和5'方向上都延伸到启动子和转录终止位点之外。未检测到除与p53基因相关的转录活性之外的其他转录活性。结果表明,与p53转录区域相邻的非转录区域在XP - C细胞中能被有效修复。这意味着除了RNA聚合酶II和相关的转录修复偶联因子之外,与转录相关的其他因子也必定在XP - C细胞的选择性修复过程中发挥作用。我们还发现,包含p53启动子的DNA片段对紫外线照射诱导的环丁烷嘧啶二聚体的敏感性几乎是周围片段的两倍,而周围片段具有预期的敏感性。

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